Although it isn’t specifically named on the cover, this issue of
GeneWatch focuses on a particular reproductive technology (or
“technique,” or “procedure,” or “set of procedures,” depending on
how you look at it and who you ask). Already you may have noticed me being oblique about this technique/technology/procedure – there, I did it again! – and throughout the issue you may
notice that even those who are intimately familiar with it have
some trouble knowing quite what to call it. As you can imagine,
the popular press hasn’t agreed on a term yet, either. A few of the
ones you’ll see most often:
Mitochondrial transfer
Mitochondrial replacement
Three-parent (or three-person) babies
Three-parent/three-person embryos
Three-parent/three-person IVF
Nuclear genome transfer
Before getting any further into that mess: What is this mitochondrial nuclear three-parent whatever-you-call it? The rest of
this issue contains plenty of explanation, as you might imagine,
but the short version is that nuclear genome transfer (this publication’s preferred term) involves removing the nucleus from
one woman’s egg and replacing it with the nucleus from another
woman’s egg.
The goal is to allow a woman with mitochondrial disease to
have a healthy child. That’s where terms like “mitochondrial replacement” come in: Mitochondria have their own DNA distinct
from nuclear DNA, so by removing the nucleus from an egg with
problematic mitochondria and swapping it into a donor egg with
healthy mitochondria, you are in effect replacing the “bad” mitochondria with “good” mitochondria. (See Stuart Newman’s article
in this issue for numerous reasons that terms like “mitochondrial
replacement” can be misleading, at times perhaps purposely so.)
If this is the first you’ve heard of all this and you have nonetheless managed to stick with me so far, you may be wondering:
What’s the big deal? Who would this really affect? And what does
this have to do with human genetic engineering? For that, I’ll turn
you over to the experts – read on.
nnn

comments and submissions
GeneWatch welcomes article submissions, comments and
letters to the editor. Please email anderson@gene-watch.org if
you would like to submit a letter or any other comments or
queries, including proposals for article submissions. Student
submissions welcome!

4 DEDICATION: Liebe F. Cavalieri
5 Introduction: What Is Mitochondrial Disease?
6 Deceptive Labeling of Radical Embryo Construction Methods Besides
being unscientific, the terms “mitochondrial transfer” and “mitochondrial replacement”
far understate the potential hazards of these techniques. By Stuart Newman
8 Providing Choices, Carefully How would mitochondrial transfer techniques
fit into the field of reproductive medicine? Interview with Paula Amato
10 The Patient Perspective In the debate over techniques for preventing mitochondrial disease, one group
is often overlooked: The people who are actually living with the disease. Interview with Sharon Shaw Reeder
14 Enabling Technology A case for moving forward – carefully – with human trials
for mitochondrial transfer techniques. Interview with Nita Farahany
16 Why Worry About Genetically Modified Babies? Here’s what’s at stake if the UK walks
back its prohibition on human germline modification. By Jessica Cussins and Marcy Darnovsky
19 Manipulating Embryos, Manipulating Truth In considering whether to
allow new embryo manipulation procedures in the UK, regulators seem more
interested in shaping public opinion than listening to it. By David King
22 Is Ooplasm Transfer Safe for the Offspring? Adapted from testimony submitted to the
FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee. By Sheldon Krimsky
23 Endnotes

Volume 27 Number 3

Image: Kenny Louie (www.kennymatic.com)

GeneWatch 3

DEDICATION: Liebe F. Cavalieri
This issue of GeneWatch is dedicated to the memory of Liebe F. Cavalieri (1919-2013).
Liebe Cavalieri was a founding
member of the Council for Responsible Genetics. An early pioneer in
nucleic acid research, Liebe was educated as a biochemist at the University of Pennsylvania. The focus of his
many scientific publications was on
DNA and DNA polymerases. His career was spent largely as a Professor
at Sloan-Kettering Institute for Cancer Research
in New York City, now
part of Memorial-Sloan
Kettering Cancer Center.
Liebe was a frequent
writer, lecturer and commentator in the public
media on the impacts
of science on society. In
the early days of genetic
engineering technology,
Liebe was among the
first scientists to alert the
general public to its potential dangers, with an
article in the New York
Times Magazine published Aug. 22, 1976 titled “New strains of lifeor death,” where he wrote
that “recombinant DNA technology
is so overpowering and far reaching
in its potential for harm that decisions on how to handle it must not
be left to scientists alone.” Later he
offered public commentary and the
seminal book The Double-Edged Helix: Genetic Engineering in the Real
World (1981 & 1985). In it, Liebe noted the high social price that often has
to be paid for scientific innovation:
We must ask ourselves whether a

4 GeneWatch

continuing process of scientific discoveries and technological applications is what we need for the advancement of mankind. We already
have an abundance of goods (whether or not they are equitably distributed), yet evidence abounds that we
are experiencing a generalised malaise throughout the industrialised
nations of the world, which strongly
suggests that we do not need more
hardware but that we should utilise
more humanely what is already at
hand.

He reminded us that we “shouldn’t
be carried away with fantasies promised by scientists and companies engaged in biotechnology research”:
Science is, however, of necessity
committed to its sources of support:
government (including the military)
and industry. They themselves are
inextricably intertwined to form
what some call the corporate state,
the single most important determinant of modern industrialised

society, characterised by a primary
drive for self-perpetuation and expansion. The corporate state controls the economy, and in so doing
it mandates, directly or indirectly,
the direction and growth of science
and technology. Economic necessity
thus presses the public to accept indiscriminately the technological system as a whole, in spite of its antisocial tendencies.

Liebe advocated an early moratorium on recombinant DNA research
until
appropriate
safety studies had
been conducted and
raised concerns that
the technology might
be used to “create an
atmosphere in which
genetic procedures
in general become
an accepted solution to many sorts of
problems – problems
which are basically
social and political.
To deal with them
at a genetic level enables us to accommodate the social
and political trends
that give rise to the
problems – but not
to overcome them.”
Following retirement from SloanKettering, Liebe moved to the State
University of New York at Purchase
and pursued his longtime interest in
mathematics to analyze procedures
for controlling the environmental
spread of foreign genes in agriculture.
nnn

Sept-Nov 2014

Introduction: What Is Mitochondrial Disease?
The mitochondria are semiautonomous organelles with their own
genomes and transcriptional machinery residing in the cytoplasm
of eukaryotic cells. Mitochondrial
cells contain 37 genes that encode
13 proteins, 22 transfer RNAs and
2 ribosomal RNAs. In contrast, the
nuclear genome consists of about
20,000 genes. Mitochondria are the
powerhouses of cells â&#x20AC;&#x201C; they store and
transmit chemical energy. They multiply when the energy needs of the
cell increases. The primary function
of the mitochondria is the generation
of the molecule ATP (adenosine triphosphate) from food sources. ATP
is often referred to as the energy currency of life.

Mitochondrial diseases are a group
of disorders that can cause debilitating, chronic illness. They are the result of either inherited or spontaneous mutations in mitochondrial DNA
(mtDNA) or nuclear DNA (nDNA),
which lead to altered functions of
the proteins or RNA molecules that
normally reside in the mitochondrial
cells. These mutations can be present
at birth or develop later in life and
cause mild to severe physical, developmental, and mental disabilities.
When mitochondria arenâ&#x20AC;&#x2122;t working
properly, they can disrupt function in
almost any of the bodyâ&#x20AC;&#x2122;s organs. Depending on which cells are affected,
symptoms may include loss of motor

control, muscle weakness and pain,
gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes,
respiratory complications, seizures,
visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infection.
Mitochondrial diseases can be
difficult to diagnose. At least one
in 8,500 of the population carries a
pathogenic mtDNA mutation, while
it is estimated that up to 4,000 children per year in the US are born
with a type of mitochondrial disease.
They are progressive and incurable,
though some treatments are available depending on the case. nnn

Techniques now exist for generating infants which, if implemented,
would constitute the first cases of
large-scale human genetic engineering. These techniques are widely referred to – by their scientist-creators
and other proponents, by journalists, by bioethicists, by members of
regulatory panels, by legislators, and
even by some critics of the procedure – as “mitochondrial transfer” or
“mitochondrial replacement.” These
descriptions are not only scientifically inaccurate, they are also easing
the way to public acceptance of these
manipulations.
What exactly are these techniques? An isolated nucleus from the
egg of one woman is inserted into an
enucleated (nucleus-lacking) egg of
another woman. Done before fertilization, it is called “maternal spindle
transfer” (MST). Done after, it is
called “pronuclear transfer” (PNT).
In fact, no transfer of mitochondria (the organelles that extract energy from fuel molecules and make
it available for the cell’s functions)
is involved in these “three-parent”
procedures. So why are they referred
to as mitochondrial “transfer” or
“replacement”?

The techniques are being promoted as a way of circumventing mitochondrial mutations, which can lead
to severe disease. It is understandable that an affected woman who
intends to become pregnant would
seek to avoid passing down this genetic predisposition to her offspring.
Methods such as MST and PNT
represent radical interventions in
the reproductive process that, if accurately portrayed, would stir fears
in prospective parents and rightly attract the attention of legislators and
regulators. The laboratory scientists
and doctors for whom these women
are clients (not patients – their own
conditions are not being treated),
thus have an interest in minimizing
the perceived scale of what they are
proposing to do.
Since it is true that nuclear genes
of an affected woman or couple will
eventually find themselves in the
presence of mitochondria from a
second woman, from the viewpoint
of the first woman the mitochondria
of her egg are “replaced.” But this is
only mitochondrial replacement in
the sense that someone who moves
into a new home may experience
“refrigerator replacement,” i.e., only

by employing a highly idiosyncratic
(and misleading) use of the term.
Focusing only on mitochondria
ignores the other significant features
of the second woman’s egg such as its
cytoplasmic and membrane composition and structure. Shifting attention in this fashion must raise questions about disingenuousness of the
methods’ proponents. In fact, the
manipulation of the second woman’s
egg (i.e., the egg that will actually be
implanted) constitutes a “genome
transfer” or “genome replacement.”
Choosing a conceptual frame based
solely on who is soliciting or paying
for the procedure (i.e., the woman
seeking to avoid passing on a genetic
predisposition for mitochondrial disease) is not motivated by scientific or
medical concerns.
In biological terms, both MST
and PNT are very much like cloning
by nuclear transfer, the methodology that produced Dolly the sheep.
Like cloning, the techniques involve
replacement of an egg’s nucleus by
a nucleus from another cell. When
cloning, the transferred nucleus is
from a differentiated cell of a fully developed animal (or potentially, a person), making the resulting organism

This is only mitochondrial replacement in the sense that
someone who moves into a new home may experience
“refrigerator replacement.”
6 GeneWatch

Sept-Nov 2014

a genetic “copy” of the nucleus donor. When undertaking MST and
PNT, the transferred nucleus is from
an egg or a fertilized egg, so that the
resulting organism will have a novel
genome. Otherwise, however, the
hazards of cloning also pertain to
MST and PNT, since the manipulations are the same. Clones tend to
die prematurely, as happened with
Dolly, or exhibit enlarged organs and
metabolic abnormalities. Some human embryos constructed by MST
unexpectedly had unbalanced chromosomal duplications (aneuploidy).
This is the case because unlike the
sorts of cellular aberrations repeatedly encountered over the course of
evolution – breaks in DNA, the unfolding of protein molecules – the
experimental combination of fragments of two broken cells generated
by cloning or the two proposed techniques have no inbuilt mechanisms
to correct the range of functional and
developmental defects inevitably associated with their construction.
It is unfortunate that few science
journalists have the training or inclination to assume a critical stance
toward the assertions of the scientists they interview. It is therefore
common to see these procedures described in the popular and scientific
press as the mere replacement of the
37 mitochondrial genes (compared
to the 20-25,000 of the nucleus). The
scientists who promulgate the transfer/replacement imagery and those
bioethicists who do the same know
better. Indeed, bioethicists should be
scrutinizing the scientists’ practice
and language as opposed to promoting their fantasies and business models. Their collusion in these deceptions is inexcusable.
Moreover, anyone familiar with
the relevant science would have
been aware, over the period during
which the techniques were being
Volume 27 Number 3

evaluated by the British Human Fertilisation & Embryology Authority
(HFEA) and the U.S. Food and Drug
Administration (FDA), of evidence
that mitochondria are not (as the
impact-minimizing refrain has it)
mere energy-providing organelles.
The very existence of mitochondrial
DNA mutations affecting hearing,
vision, pancreatic function and neuromuscular activity (the justifications of the entire enterprise), would
be enough to tell us this. Indeed, in
the past two years the evidence for
the non-passivity of the mitochondria has become inescapable. Since
mitochondria are active participants
in cell function and organismal development, integration among coevolved nuclear and mitochondrial
systems would contraindicate arbitrary mixing and matching. (The engines of a Jaguar and a Rolls-Royce
do essentially the same thing, but
they are not interchangeable.) This
adds an array of hazards to MST and
PNT that go well beyond those they
share with cloning.
A prospective child made by MST
or PNT would be the result of an
evolutionarily unprecedented experiment with known, or easily anticipated, hazards. Juxtapose this
against the fact that the biological
identity and long-term health of the
three biological parents undertaking

MST or PNT are not directly at risk
in the procedures. It is, therefore,
entirely unwarranted to make their
perspective (or more specifically that
of the nuclear gene donor) the one
from which the procedure is judged,
thereby allowing the techniques to
be characterized as being of minimal impact. Rather, the perspective
of the individual brought into being
by the procedures should be paramount. Combining fragments of two
damaged eggs to produce a human
embryo is, despite the rhetoric of
mitochondrial “transfer” or “replacement,” large-scale manipulation of
nuclear genes. Its backdoor admittance to the repertoire of assisted reproduction techniques in the guise of
being a trivial tweak bodes ill for future attempts to regulate gene transfer methods for any other purpose.
A kind of omertà among scientists and bioethicists has prevented
a significant number of them from
representing to the HFEA and FDA,
and the press, the gravity of these alterations. But the health implications
and the eugenic outcomes these procedures would enable are too great to
ignore.
nnn
Stuart A. Newman, Ph.D., is Professor of
Cell Biology and Anatomy at New York
Medical College.
GeneWatch 7

Providing Choices, Carefully
How would mitochondrial transfer techniques fit into the field of reproductive medicine?
Interview

with

Paula Amato

Paula Amato, MD, is a board-certified
Reproductive Endocrinologist and an
Associate Professor in the Department
of Obstetrics & Gynecology at Oregon
Health & Science University.

As you know, this issue of GeneWatch focuses on “nuclear genome
transfer,” or “mitochondrial transfer,” or “mitochondrial replacement,” or whatever you prefer to
call it. Some of the other contributors object to the approval of this
technology on ethical or medical
grounds. So: What are they missing?
What’s the best argument for going
forward with these procedures?
Right now there’s no cure for mitochondrial disease, but this could

8 GeneWatch

theoretically be an avenue for prevention. These children, as you know,
have very devastating diseases, and
they usually die at a young age. The
other methods we have to try and
prevent it – like preimplantation
genetic diagnosis – don’t work very
well for mitochondrial disease because of the way mitochondrial DNA
is inherited. So this would potentially
offer a way of preventing the disease
in children. It has been shown to be
effective in monkeys – and I would
agree that monkeys aren’t people, so
it certainly doesn’t guarantee that it
would be safe in humans. I think it’s
reasonable to do as many studies as
we can using human tissues in vitro before we try it in vivo. But ultimately, the reality is that we probably
won’t know until we actually do it in

humans, transfer an embryo and create a baby. And that’s true for a lot
of the technologies in reproductive
medicine. We’ve always tried to do it
first in animals and then in vitro in
humans, but ultimately until we do it
in humans we’re never quite sure that
it’s going to be safe.
Would you say this is something
fundamentally different compared
to other assisted reproductive procedures used today?
A lot of the process is quite similar.
The whole ovarian stimulation and
the embryo transfer part would be
similar. The difference is the technical aspect of taking the nuclear DNA
out of one egg and transferring it into
a donor egg that has had the nucleus

Sept-Nov 2014

removed. That part is novel; it has
not been done in humans before. I
mean, we’ve done it in human eggs
and made embryos in the lab, but
we have not created a baby. In some
sense, it’s kind of similar to a donor
egg, where you replace the entire
genome, nuclear and mitochondrial
DNA. It’s similar to that, except that
this requires more manipulation of
the egg.
Do you have concerns about the
safety of these procedures, either
for parent or child?
I do, more so for the children. I think
the process that the parent undergoes – the in vitro stimulation, retrieval, and transfer – we’ve been doing that for more than 35 years. There

per se, it’s really about prevention of
disease. I think that risk always exists, but I don’t think it’s sufficient
reason not to pursue this technology.
Technology can always be misused,
whether it’s medical technology or
military technology or computer
technology, but I don’t think that’s
a reason not to use it for positive
purposes.
You practice as a reproductive endocrinologist, right? So if a woman
came into your practice and said,
“I have mitochondrial disease and
I want to have a baby using one of
these procedures,” how might you
respond? Obviously that’s making
some assumptions since it’s not legal at this point …

“I don’t think in general that people
ought to be making reproductive
decisions for other people.”
are some risks with that, but they are
relatively safe procedures. I think
the big unknown is the result for the
child. And of course I do have questions, and I worry about whether it’s
going to be safe, but I think there is a
strong enough reason to try it and to
find out, after appropriate numbers
of studies have been done.
It’s pretty hard to argue that these
procedures qualify as “eugenics,”
but do you have concerns about
this technology leading to something like that in the future – to use
the media’s favorite term, “designer
babies”?
I think that’s always a concern, but I
don’t think this technology is unique
in that regard. It is not enhancement
Volume 27 Number 3

Right – that would be a barrier! I’d
explain that currently, in the United
States anyway, we can’t really do that
procedure because it’s not approved
by the FDA. We’d like to do a clinical
trial, but we’re waiting to hear from
the FDA on that.
But assuming that at some point it
was approved, it would be similar to
other medical or reproductive procedures: We would speak with the
patient and make sure she has given
informed consent about all the potential risks to her or her baby; we
would offer her counseling; and we
would certainly do it, at least initially, under the auspices of the IRB as
part of a research protocol, since we
would want to gather as much data
as possible to make sure that it’s safe.

Do you have a sense of who would
be using this?
I think initially it would be women
who are carriers of the mutation.
Most people don’t know they are carriers until they have a child who is
diagnosed with a mitochondrial disease. The mothers of those children
are the ones we would be offering this
technology to. It’s not a very common disease, so I don’t expect the
uptake to be great, just because the
numbers of eligible patients probably
wouldn’t be great. And there’s always
the cost issue; IVF in general is kind
of an expensive procedure, so there
probably will be issues of access, just
as there are for anyone using IVF.
There are other potential applications for this technology. Aging eggs
are thought to have acquired mitochondrial mutations, so in the future,
if this is shown to be safe in women
who are carriers of mitochondrial
gene mutations, this might potentially be a therapy for age-related
infertility.
Given the cost issue, and the possible safety issues, some people
might ask: Why not just adopt?
That’s an easy thing for people to say,
and infertility patients hear it all the
time. I really think it’s unfair. It’s fine
for people to make their own reproductive choices, and I think adoption
is a great thing, but I don’t think it’s
unusual or selfish in any way to want
to have a genetically related child. I
think it’s a basic human instinct, and
I don’t think in general that people
ought to be making reproductive decisions for other people.
nnn

GeneWatch 9

The Patient Perspective
In the debate over techniques for preventing mitochondrial disease, one group is often
overlooked: The people who are actually living with the disease.
Interview

with

Sharon Shaw Reeder

Sharon Shaw Reeder was diagnosed
with mitochondrial disease in 1999. She
has been a member of the United Mitochondrial Disease Foundation Board of
Trustees for over a decade and was appointed to the FDA’s first Mitochondrial
Patient Advisory Committee.

I noticed something while reading
up a bit on this issue, and I wonder
if you’ve noticed it too: In the popular press and in ethical debates
about these procedures – so-called
“mitochondrial replacement” or
“three-parent babies” – the people
who actually have mitochondrial
disease are often overlooked.
Yes, and I appreciate your understanding of that. Living with mitochondrial disease is like trying to
find corners in a round room. It is the
most complicated disease out there.
Mitochondria are responsible for
90% of the energy produced in each
cell in our body. This translates into
everything we do – how we walk,
how we talk, how we chew, how we
digest, how our brains function – everything in our body requires energy, and when there is a defect in the

10 GeneWatch

mitochondria, all kinds of stuff happens. So for people living with mitochondrial disease, it can look like five
to ten different illnesses. You can’t
just go to one doctor; I have a team
of 14 different doctors. The best analogy I have heard is trying to run your
house on two batteries. You just don’t
have enough energy to run your body
properly.
When I was diagnosed, I got the
message that I should get my affairs in order because I might not be
here in a couple of years. That was
13 years ago, and obviously I’m still
here. There is no treatment, and there
is no cure, but there are therapies
which help to manage the symptoms.
So what I did was get busy. That was
my therapy, to become a part of the
solution instead of just wallowing in
the devastation of being diagnosed
with a chronic and progressive disease. I mean, none of us are getting
out of here alive, right? We all get
something.
My passion comes from this
point: Mitochondrial diseases are
not rare. But it feels sometimes sort
of like Horton Hears a Who: “We’re
here! We’re here!” One in three or
four thousand have mitochondrial

disease, and one in two hundred carry the possibility of passing on defective mitochondria, but there is very
little money going into primary mitochondrial research.
We’re early on in the timeline of
understanding this disease. First they
identify the problems, then they can
understand the symptomology of it,
then they can develop testing for it,
and then the hard part: Getting everybody to know what it is, and creating treatments and cures.
And it probably doesn’t help that
it’s such a complicated disease.
You know, if you have cancer, we understand that and we say “what kind
is it?” We know there are over 200
different types of cancer, and there’s
pretty much a test for every kind of
cancer out there. Well, with mitochondrial disease, if you ask “which
kind?” … there are literally tens of
thousands of different kinds, because
mitochondria have their own set of
DNA. So when I say this is a complicated disease, it’s times ten.
I have adult onset mitochondrial
disease, which means it didn’t hit me
until I was 19. All of my muscles are

Sept-Nov 2014

affected, my eyes, brain, digestion
but for me, it’s been a long, slow progression. But nevertheless it is progressing. I am no longer able to do
any type of activity which requires
too much endurance or strength, so
daily activity is now challenging. For
the kids that are born and you can
tell something is wrong very early,
it’s faster, and the mortality rate is
50%. At this point, we are probably
of more use to researchers than they
are to us. It’s not their fault, it’s just
where we are at this point.
You’ve been working on this for
13 years. Is there anything in that
work that makes you feel especially
hopeful?
The United Mitochondrial Disease
Foundation is one of the very rare
nonprofits out there ... we do everything all under one roof: awareness,
raising money for research, lobbying
on the Hill and giving support and
education to our families and community. It’s exciting to see where
we are today compared to 13 years
ago, and I am thrilled to know that
we’re pushing the needle, we’re making progress, and more people know
what mitochondrial disease is.
The really important thing right
now is that if we put more research
into primary mitochondrial medicine, we could actually help not just
those with mitochondrial disease, but
many other diseases as well. There
are links to Parkinson’s, Alzheimer’s, childhood cancers, diabetes,
lupus, autism spectrum disorders …
there’s an element of mitochondrial
dysfunction in all of these other diseases. We have been trying to put a
consortium together at NIH to bring
together different types of research,
to say to everyone already looking
into the importance of mitochondrial function – cancer researchers,
Volume 27 Number 3

Parkinson’s researchers, Alzheimer’s
researchers: Instead of all working in
our own little cubicles, how about we
all get together and collaborate on
our research on mitochondria? Forget about two birds with one stone,
you’re talking about at least eight major disease populations being helped.
We are stronger if we pull together.
What do you think about so-called
“mitochondrial replacement” or
“three-parent babies” – procedures
that aim to prevent mitochondrial
disease by modifying the oocyte?

actual “designer babies”? Of course I
wouldn’t want that.
But that’s not my issue with it. My
issue is this: Can’t we please take the
research, the effort, the brilliance,
the money that’s being spent making
sure that future generations won’t
have mitochondrial disease, and help
those of us that are suffering right
now?
You’re putting all of that money
into this procedure, and we can’t
even get the folks that are suffering
now a proper diagnosis, let alone
treatment. There are a lot of patients
that are suffering right now. For me,

“This kind of research we’re talking
about, on these procedures to help
future generations sometime down the
road, will cost millions and millions of
dollars. Meanwhile, there are so many
families who need help right now and
aren’t getting it. It’s maddening to me.”
I think that the science that is in
place to primarily affect the transfer so that a mitochondrial mother
– a potential mother who is a mitochondrial patient, who doesn’t want
to pass on the disease to her unborn
child – I think the science is brilliant.
I think this is the kind of science
and research that helps future generations. I’ve heard all of the hoopla
and the opinions about the moral
and ethical issues, I’ve heard it called
“designer babies,” I’ve heard the fear
and concern about it, that because
we’re manipulating the genetics to
make sure the baby won’t be born
with mitochondrial disease, how can
we know that’s not going to lead to

it is so out of balance. We’re not helping the population that’s living with it
now. We’re not helping the children
that are dying from it now.
I know I’m not being very diplomatic here, but it just seems a little
backwards to me.
Where does that leave women with
mitochondrial disease who want to
have a baby?
I was pregnant and had mitochondrial disease and didn’t know it at the
time, since I was not diagnosed until
one year after giving birth to my son.
Being pregnant made my disease
progress and I got weaker because of
GeneWatch 11

the strain on my body. It put me in a
wheelchair at the time. So if I was to
sit with a woman with mitochondrial
disease who was thinking about getting pregnant, I would counsel her to
really give that a long thought. I understand that we all have the right to
procreate, but I might suggest she
look into adoption or fostering. As a
woman who has been through this, I
know the risk she might be putting
herself into.
Put it this way. U.S. News and
World Report did a story when my
son was about a year old, and they
asked me the question: Had I known
I had mitochondrial disease, would I
have gotten pregnant and had a baby?
And I could easily say no. Am I glad
that he’s here now? Absolutely. But
no, I would not have done that. The
other point is passing it on to him. As
a parent, I don’t feel like we have that
right to be selfish in that way: That
my need to procreate and pass on my
genes is stronger than the risk that I
might pass it on to my child. That’s
a very personal feeling, but I would
find another way to love something,
rather than to possibly pass on a lifethreatening chronic illness.
Say a nuclear genome transfer
procedure was available, so that
through a surrogate you could have
a child with some of your DNA but
much less chance of inheriting mitochondrial disease. In retrospect,
would you have considered going
that route?
The answer then would have been
maybe, but my answer now is no, not
after living day in and day out with
my symptoms. The possibility does
not personally outweigh the risks.
The procedure does not ensure that
there isn’t still a risk to the child. I
couldn’t be that selfish. It’s not that
important to me to procreate at the
12 GeneWatch

risk of passing on known suffering.
Also there are not enough doctors
right now to help our population
let alone a population of new mitochondrial children; whether they are
symptomatic or not they will still
need to be followed.
Let me put it to you like this: What
you’re asking is, “Sharon, if there’s a
great chance that the baby would be
OK, would you do this?” Because I’ve
lived with this thing – because my
whole life changed after my diagnosis and all of my plans changed, and
forget Plan B, now I’m on Plan W – I
cannot justify putting money into developing procedures that are only going to help someone down the road.
People right now can’t get treatment,
they can’t even get proper diagnosis.
It’s like spending fifty grand on furniture and rugs when not only have
I not built the house yet, I don’t even
know where I’ll live. I just think that
we’re way ahead of ourselves and forgetting about a population that’s here
right now, and in need.
Here’s an analogy. What if someone was to say, “We’re going to put
all our money into genetically engineering rice so that 10 or 20 years
down the road we can feed all the
hungry people in the world.” I would
say: How about we put that money to
use helping people who are starving
today?
This kind of research we’re talking
about, on these procedures to help
future generations sometime down
the road, will cost billions of dollars.
Meanwhile, there are so many families who need help right now and
aren’t getting it. It’s maddening to
me.
You were part of the FDA hearings
in February that discussed these
technologies, as a patient representative. Was there anything that
surprised you during this process?

Was there anything you found particularly disturbing or compelling?
I think one thing that surprised me
was that some of the comments
around the table were similar to what
I just said, along the lines of “Given
where we are on the spectrum of understanding this disease, it’s so premature to be doing this. How about
we just offer other solutions to a
mother who wants to have a baby?”
I was pleased that the people
around the table learned more about
the complexity of mitochondrial
disease, and that while the procedures sounded simpler, the disease
itself isn’t. And even with what we
already know, there’s still so much
to learn. I was pleased to know that
these experts sitting around the table
were still learning about the disease.
I think that the way the media spun
these procedures was wrong – it’s
not “designer babies.”
And I think there was a compassion around the table, a desire to help
people.
Did you get that from everyone,
regardless of their position on the
procedures being debated?
I did. There was really a compassion
to help disease populations. And I
appreciated that. There was really a
genuineness there to think through
the issue and be careful and ask questions, and I appreciated the process
the FDA put together to ensure that
happened.
The other thing I got at the FDA
hearings was that the passion and enthusiasm from these geneticists that
figured out the procedure was unbelievable, and it was genuine. I just
wish more of them would have that
enthusiasm for patients that have mitochondrial disease right now.
nnn
Sept-Nov 2014

From the Council for Responsible Genetics

The
GMO
DecepTiOn
What You Need to Know about the Food,
Corporations, and Government Agencies Putting
Our Families and Our Environment at Risk

edited by Sheldon Krimsky and Jeremy Gruber
Foreword by Ralph nader

“If you do not understand why there is so much opposition to GMOs, nationally and internationally,
this book is the place to start.”
—Marion Nestle, professor of nutrition, food studies, and public health at New York University and
author of Eat Drink Vote: An Illustrated Guide to Food Politics
“This eye-opening collection of essays by numerous experts lays bare what global corporations like
Monsanto are attempting to foist upon us, as well as how activists around the world are fighting
back to preserve our children’s future.”
—Dick Russell, environmental author
“The GMO Deception is the most comprehensive resource covering all areas of this complex topic.”
—Ken Roseboro, editor and publisher, The Organic & Non-GMO Report

Nita A. Farahany, PhD, JD, is the Director of Science and Society and Professor of
Law and Philosophy at Duke University.
She was appointed in 2010 to the Presidential Commission for the Study of Bioethical Issues and continues to serve as a
member.

The technology we’re discussing
– “nuclear genome transfer,” or
“mitochondrial transfer,” or “mitochondrial replacement,” or “threeparent babies,” whatever you prefer
to call it … actually, first off, what do
you prefer to call it?
That would depend on which technique we’re talking about. I don’t ever
use “three-parent babies,” because
that’s just wrong. It takes far more to
be a “parent” than mere contribution
of mitochondrial DNA. “Mitochondrial transfer” is a more general term,
which captures some of the different
techniques.
You’ve talked about the need for
adequate regulation of these technologies, but it seems safe to say
you’re also an advocate of moving
forward with it. What sort of ethical or regulatory framework do you
think is needed before the technology can be adopted?
I wouldn’t say I’m an “advocate” for
anything. I think that the process
that the HFEA (the UK’s Human Fertilisation and Embryology Authority) used to study the safety and efficacy of mitochondrial transfer was
14 GeneWatch

a pretty comprehensive approach to
understanding the scientific issues.
And safety and efficacy are ethical
issues and independent criteria to
consider. From a safety perspective,
I think the data justifies moving to
very small-scale clinical trials. But
I’d want very careful oversight and
follow-up of those trials.
I’d want to make sure that we carefully think about research participant
selection, agreements about longerterm follow-ups so that we can be
able to see what happens later on.
And we would have to think about
some of the possibilities that have
been raised – for example, if all of
this is done using an IVF procedure,
whether or not selecting for male embryos in the first generation makes
sense, because then you don’t have
the same concerns about the implications for future generations as far as
passing on mitochondrial DNA. So I
think we’d want to think very carefully about how we structure those
studies, but we’re at a stage where
the data is strong enough to move toward determining how to best structure small-scale clinical trials.
Since there haven’t been human
clinical trials yet, so far the safety
studies have been on rhesus monkeys – is that right?
Yes, and also mice.
And you don’t think more is needed before moving to human clinical
trials?
Sept-Nov 2014

With any reproductive technology,
for some people there will never
enough data to justify a move to human clinical trials. And yet, we have
as much if not more data than we did
when we moved to human clinical
trials for IVF. I think we’re ready, particularly given the gravity of the consequences from not moving forward,
to move to small-scale clinical trials.
Different regulatory bodies around
the world have chosen different
places to draw the line on what
should and shouldn’t be allowed as
far as technologies that could result
in human germline modification.
Where would you draw the line?
I’m comfortable with mitochondrial transfer at this stage, but I
would draw the line and say that we
shouldn’t be doing nuclear modification. Some of the data shows that
with mitochondrial replacement,
some of the mitochondrial abnormalities are actually coded within the
nucleus, so the procedure might be
more successful if it included nuclear
changes. Nevertheless, I would limit
it, at least right now, to only making
mitochondrial transfer and not actually making nuclear changes.
You say you’d limit it “right now”
– is there something that might
change that?
I could imagine at some point in the
distant future we might consider
nuclear modifications as well, it’s just
not something that’s anywhere close
to being on the table.
So your concerns about modifying
nuclear DNA are more about the
science than about ethics?
I don’t think it makes sense to draw
Volume 27 Number 3

bright lines between the science and
the ethics. Good science is responsible science, so they go hand in hand.
Scientifically, we’re nowhere close to
being able to reliably make nuclear
modifications. I think for that reason,
and for additional ethical concerns,
staying out of nuclear modifications
for now is the right approach. Could I
imagine a future in which there were
some nuclear modifications that we
permitted? I could imagine such a future, but a lot of things would have to
change between now and then.
In the meantime, with “mitochondrial transfer” – these technologies
that could help prevent mitochondrial disease – am I right in understanding that this could greatly
reduce the chances of passing on
mitochondrial disease, but would
not be able to altogether eliminate
mitochondrial disease without also
modifying the nuclear DNA?
So, two things. One is: Some people
don’t have such a high degree of abnormality that it would require them
to have mitochondrial transfer. Low
levels of abnormality could still be
carried on generation to generation,
and that could end up with one generation being disproportionately affected – through no intervention on
our part, right, just because a fact of
nature is that some people have a mitochondrial abnormality, and it may
get passed on in higher concentrations to some offspring rather than
other offspring. So you’re still going
to have some mitochondrial abnormalities in the population.
As for the people who have some
of the mitochondrial abnormality
that arises from problems within the
nuclear DNA, you’re right: These
techniques wouldn’t eliminate that.
They do bring it down sufficiently to
a level where you don’t see the kind

of health consequences you would
otherwise.
Some are uneasy with these technologies because of the possibility
that it enables “designer babies” or
a sort of eugenics. But as I understand it, you look at a technology
like this as more a matter of individual choice.
I think one of the things people
worry about with eugenics is statesponsored eugenic action. That is
very different from private individuals making private choices, which
will vary from person to person.
You know, not everyone chooses a
child with blond hair and blue eyes,
one reason being that many people
want children who look like them.
Of course, this is in the world of
nuclear DNA modifications, which
I think is far off. But imagining that
future, if it’s private individuals making private choices, it’s going to lead
to a much greater diversity of choices
than we’d expect in a state-sponsored eugenic society. So I have less
concern than some people do about
dystopian eugenic futures, because
I think that presupposes a very different approach to decisions about
reproduction.
So in other words, the problem
would be not the technology, but
how it’s used and how it’s regulated?
I think technology is neither good
nor evil; it’s how we use it that determines its normative value. The
same technology can be put to good
or evil purposes. What I would feel
comfortable with is enabling technology to proceed, but ensuring that
we have a prudent approach to overseeing that technology to safeguard
against misuse.
nnn

GeneWatch 15

Why Worry About Genetically Modified Babies?
Here’s what’s at stake if the UK walks back its prohibition on human germline
modification.
By Jessica Cussins

and

Marcy Darnovsky

The terms “genetically modified
babies” and “designer babies” are
attention-getters. But beyond the
catchy sound bites, what do they really mean – and are they something
we need to worry about?
Unfortunately, with the technical
capacity to engineer inheritable traits
growing quickly, and with the United
Kingdom possibly on the verge of
loosening its law in order to allow a
limited form of inheritable genetic
(germline) modification, there is ample reason for concern.
The proposed policy change in
the UK would permit licensed fertility clinics to use a biologically radical technique referred to by terms
including “mitochondrial replacement,” “nuclear genome transfer,” and
“three-person IVF.” This procedure
would produce modifications in every cell of any resulting children, and
in subsequent generations as well.
In this article, we will use the term
“nuclear genome transfer,” as it is the
most technically accurate of the various terms.
The technique is proposed as a way
for women affected by a particular
subset of severe mitochondrial disorders to have children who are not
affected and who are mostly genetically related to them. The researchers
promoting it, and some people with
mitochondrial disease, have pointed
out that they would not be using
the technique to produce “designer
babies.” Understandably, some are
16 GeneWatch

perplexed or offended by those who
object to the procedure on that basis.
But these advocates of nuclear
genome transfer have missed a key
element of the case against it. Those
of us who oppose it on social and
policy (as well as safety) grounds
aren’t arguing that it would in itself
create enhanced humans with specified traits. Our concerns fall into two
categories. The first is that an exception to the widespread prohibitions
against human germline engineering
will open the door to other efforts to
modify inheritable traits – that nuclear genome transfer is the thin end
of a wedge that would lead to a world
of genetically altered human beings.
The second set of concerns focuses
on safety. This technique, like other
forms of human germline modification, is in fact both medically unnecessary and profoundly risky to the
children it would produce. Let’s look
briefly at each of these sets of concerns, starting with the social and
policy issues.
If the UK permits nuclear genome
transfer to move ahead, it would
break a widely observed prohibition
that has been respected by scientists
globally, and codified as law in more
than 40 countries and several international treaties. No other country
in the world has ever explicitly sanctioned human germline modification. Just as with human reproductive
cloning, it is explicitly prohibited in
the Council of Europe’s Convention

on Human Rights and Biomedicine,
and considered to be “contrary to human dignity” in UNESCO’s Universal
Declaration on the Human Genome
and Human Rights.
Because human germline modification is illegal in the UK, proponents
of nuclear genome transfer have
elected to work toward carving out
a narrow exception that would allow
their particular manipulation methods to be implemented. A change in
UK law to allow “mitochondrial replacement” in fertility clinics, without any required follow up of the resulting children, would inescapably
set both a global policy precedent
and a biotechnological precedent for
the scientific community. If the UK, a
country with one of the world’s most
highly developed biomedical sectors,
believes this is the way forward, it
would shift the scales and threaten
the current international near consensus on the responsible use of genetic technologies. The UK would
become an outlier, and would have to
carry the burden as well as the benefit
that comes with that position. And as
David King explains in this issue, the
way this policy process has unfolded
– with numerous irregularities, misrepresentations, and cherry picking of scientific evidence – deepens
our concerns that approval would be
used as a wedge issue.
In the United States, a committee
of the Food and Drug Administration
held a day-long hearing in February
Sept-Nov 2014

2014 to discuss human germline
modification for the prevention of
the transmission of mitochondrial
diseases or for the treatment of infertility. Most of the experts on the
committee came away deeply skeptical about the issues they were mandated to consider: the techniques’
safety, efficacy, and necessity.
The United States is one of the few
countries with an advanced biomedical sector that does not have any law
against human germline modification. This means that if nuclear genome transfer were allowed, it could
be used for any purpose. Unfortunately, there are concrete reasons
to worry about this sort of “mission
creep.” One is that Shoukhrat Mitalipov, the U.S. researcher most notably involved with advocating for
nuclear genome transfer, has made
it very clear that he’d like to see the
technique used in efforts to treat agerelated infertility (in spite of the fact
that, as several experts on the FDA
committee noted, there is no clear
evidence of any relationship between
mitochondrial insufficiency and infertility). Mitalipov has been quoted
in several articles looking forward
to nuclear genome transfer being
quickly adopted in fertility clinics
around the country and the world.
He has applied for a patent on his
version of nuclear genome transfer,
and has established a company presumably to commercialize its use as a
fertility treatment.
Would there also be pressure to
permit human germline modification techniques that would alter
nuclear genes, in an effort to specify
physical, behavioral, or cognitive
traits? There is reason to believe
there would be – in fact, a small but
disturbing number of prominent scientists and futurists have advocated
precisely for this vision. For example,
a report produced on the basis of the
Volume 27 Number 3

1998 UCLA conference “Engineering
the Human Germline” argued for the
“open exploration” of “human germline engineering.” Currently, new
precision gene editing techniques
such as CRISPR have some scientists
excited about the possibilities for the
genetic modification of human embryos or adults. Will these new techniques, which will open the door to
much more precise changes, be considered less drastic if nuclear genome
transfer has already been approved?
Human germline modification
would be of profound consequence
whether it were to “succeed” or “fail.”
If efforts to engineer the traits we
pass on to future generations succeed, they could exacerbate existing
inequalities – or even introduce new
forms of inequality – based on the
real or perceived superiority of those
whose genes had been tweaked. And
we could find ourselves trapped in
a kind of genetic arms race, which
could lead to social disruption on a
possibly massive scale.
What if such efforts fail? Germline modification in animals typically
involves dozens or hundreds of nonviable offspring. If human germline
modification efforts yield similar results, what would become of the people created? Who would be accountable for bouts of unnecessary human

experimentation gone wrong?
With nuclear genome transfer, the
policy, social and safety issues are
inextricably entangled. Some proponents both insist that it would not
create genetically engineered babies,
and are actively trying to redefine genetic modification completely so as
to exclude this particular technique.
The U.K. Department of Health wants
to make a distinction between changes to mitochondrial DNA (mtDNA)
and nuclear DNA (nDNA), arguing
that only the latter really constitutes
genetic modification. While there are
obvious differences between the two,
this redefinition has no basis in scientific reality. mtDNA and nDNA are
in continuous interaction with each
other and changes to mtDNA would
cause inheritable changes to every
cell of a resulting person.
The notion that nuclear genome
transfer is as non-consequential as
“changing a battery” is entirely misleading. Scientists have known for
some time that mtDNA have pervasive effects. A recent article in New
Scientist reviews the accumulating
evidence. The overall picture is now
so clear that the magazine’s editors
have just reversed their earlier support for “three-parent IVF,” and acknowledged that they “may have seriously underestimated the influence
GeneWatch 17

that mitochondria have” and that in
fact, “children conceived in this way
will inherit vital traits from three
parents.”
Which brings us to the second
category of concerns about nuclear
genome transfer. Like reproductive
cloning and germline modification, it
is scientifically interesting, but applying any of these techniques to human
beings will never be medically necessary, and would pose serious safety
risks both known and unknown.
Nuclear genome transfer involves
the removal and reinsertion of a
nucleus from its own egg cytoplasm
to that of another woman’s. The procedure changes the environment for
the nucleus, and introduces it to 37
new genes with which it will need to
work in order to carry out every activity moving forward. The impacts
of combining genetic material from
three different people are entirely
unknown, but it is certain that it will
have an impact.
Safety concerns for women would
include all the short- and long-term
risks of egg extraction and IVF. And
as members of the FDA committee
pointed out, pregnancy and childbirth are often in and of themselves
risky for women with serious mitochondrial disorders.
Safety concerns for resulting children would include epigenetic harm
from the invasive procedure of removing and reinserting the nucleus,
and “mismatch” between the nuclear and new mitochondrial DNA,
which could disrupt critical biological functions. Additionally, even tiny
amounts of carryover of mutated mitochondria from the first egg could
lead to the occurrence of mitochondrial disease through preferential
replication.
Questions of efficacy are paramount as well, given that the vast
majority of mitochondrial diseases
18 GeneWatch

actually originate with mutations
in nuclear DNA, and could not be
helped by these techniques. Further,
the few women who would be candidates for nuclear genome transfer –
estimates are on the order of a dozen
or so a year in the UK – have much
safer options for having healthy and
genetically related children.
Some proponents of nuclear genome transfer try to hitch it onto the
coattails of the reproductive rights
and justice movements, and to justify
risky experiments as allowing women
to make informed, personal choices
about reproductive technologies.
But first and foremost, these are biologically extreme technologies that
would use women’s and children’s
bodies as ground zero for their experiments. It is women and children
who will be encouraged by soothing
words and images, and then be asked
to bear the risks while a fertility clinic
collects an estimated 80,000 pounds
for each attempted treatment.
Even with conventional treatments that are far less biologically
extreme, the fertility industry does
not have a good track record of putting evidence-based information before its customers. And the lack of
required follow-up that has already

been built into the UK’s proposed law
does not bode well for women’s ability to make informed decisions about
the safety or efficacy of this option,
or to compare it realistically with its
safer alternatives, which include preimplantation genetic diagnosis, egg
donation, and adoption.
So, what is really at stake if the UK
changes their law to allow a form of
human germline modification into
fertility clinics? Primarily, the health
of women and children, and the integrity of the widespread international agreement against the most
dangerous human biotechnologies.
And also, perhaps, the shape of the
human future.
nnn
Jessica Cussins is a project associate
at the Center for Genetics and Society, and a regular blogger at Biopolitical Times, Psychology Today, and
Huffington Post.
Marcy Darnovsky is executive director at the Center for Genetics and Society, and writes widely on the politics
of human biotechnologies.

Sept-Nov 2014

Manipulating Embryos, Manipulating Truth
In considering whether to allow new embryo manipulation procedures in the UK,
regulators seem more interested in shaping public opinion than listening to it.
By David King

The UK experience of the process of legalization of “mitochondrial replacement techniques” has
been an object lesson in how a welloiled technocratic machine can manipulate public opinion in order to
achieve the desired result or simply
ignore negative public responses.
In the UK, reproductive technologies are regulated by the Human Fertilisation and Embryology Act, which
was last updated in 2008. The Act prohibits the implantation in a woman
of embryos produced by any means
other than fertilization of an egg by a
sperm. However, because the possibility of ‘mitochondrial replacement’
was envisaged at that time, there is a
provision which allows the Secretary
of State to make regulations permitting the use of such embryos, on a
case-by-case basis. We are now at
this stage, and it is expected that the
government will publish the regulations this autumn. It is important
to understand that there will be no
significant parliamentary debate on
the regulations or any possibility of
amending them: the procedure simply involves a one hour discussion by
a committee which can only approve
or reject regulations. In essence, this
is a rubber-stamping procedure.
Unlike nearly every other European country, the UK has not signed
the Council of Europe Convention
on biomedicine and human rights,
which prohibits any intentional
changes to the human germ line.

Volume 27 Number 3

How to get the answer that you
want
The process of legalization of
‘mitochondrial replacement techniques’ began in the spring of 2012
with a report by the Nuffield Council
on Bioethics, an independent academic body funded by the Nuffield
Foundation.
As expected, the Council approved
the use of these techniques. Its main
innovation was to decide that the
techniques constituted a form of manipulation of the human germ line,
something that elite opinion had previously denied. In recognizing that
this crucial ethical line was being
crossed, the Council insisted that any
attempt to manipulate nuclear DNA
through genetic modification would
require further ethical consideration.
Following the Nuffield Council report, the HFEA announced its main
public consultation on the ethical aspects in mid-2012. U.S. readers will
probably look upon the UK regulatory system, and the existence of the
HFEA, as a good thing, at least in
comparison to the lack of statutory
regulation in the U.S. The existence
of the HFEA plays a crucial role in
reassuring the public that these difficult ethical issues are being responsibly considered by the powers that be.
But in reality, although the HFEA is
obliged to maintain some degree of
separation between itself and the IVF
industry and entrepreneurial scientists that it regulates, in terms of its
ideological position, the HFEA is in

complete concord with those industries. In fact, its current head of policy was formerly director of the Progress Educational Trust, a body set up
in the 1980s that has always argued
for liberalization and acceptance of
every new technology.
The HFEA has become practiced in
using public ‘consultation’ to advance
the use of such technologies and to
weaken ethical restraints upon them.
In general, the HFEA is well ahead of
public opinion, but only on one occasion has it failed to carry the public with it. That was in 2003, when it
issued a consultation arguing for the
legalization of sex selection for social
reasons. An extremely strong negative public response forced HFEA to
abandon that position.
HFEA’s consultation documents
are written with a technocratic bias
that makes little effort towards evenhandedness. In recent years it has
become increasingly overconfident.
For example, in 2009 the new chair of
the HFEA, Lisa Jardine, announced
in a newspaper interview that she
was in favor of paying egg donors
for their services in advance of the
HFEA’s consultation. In this case it
has simply ignored the results of the
consultation.
The HFEA’s manipulation of the
consultation process had two main
elements: (i) misleading scientific
information, and (ii) biased ethical
discussion.
Bad science
GeneWatch 19

The key piece of scientific misinformation that was crucial to the ethical misunderstanding of these techniques was the statement, endorsed
by major scientific institutions, that
mitochondria act as mere “batteries”
for cells, and that mutations in mitochondrial genes have no effect on an
individual’s identity. The statement
made an analogy with a laptop computer; its batteries do not affect the
programs or data on the laptop. The
purpose of this endlessly-repeated
statement was to minimize the ethical significance of the changes to the
germ line involved. (In these discussions, ‘identity’ was never clearly
defined, but the general impression
given was that it referred to visible
physical differences, and perhaps
personality.)
This piece of scientific nonsense is
a classic example of the reductionist
models of biology which dominate
public debate and are clearly used by
advocates of new technologies to manipulate the debate. Living organisms
are simply not like computers: they
are complex, whereas computers are
merely complicated. Even were it
true that the functions of mitochondria are restricted to generating ATP,
the idea that energy metabolism can
somehow be isolated from the rest of
the physiology of the organism is biologically laughable. This is the same
mentality that leads synthetic biologists to claim that they can separate
and redesign different ‘modules’ of
cellular function. One might imagine
that such ambitious scientific claims
would be backed up by detailed scientific evidence, but insofar as it is possible to determine the origin of what
has now become an urban myth, the
claim is entirely unsupported. The
main quoted ‘scientific’ reference for
the claim is a submission by those
two august medical authorities, the
UK Medical Research Council and
20 GeneWatch

the Wellcome Trust, to the Nuffield
Council enquiry, which contains no
scientific references whatever for this
claim.
In reality, energy metabolism is
entangled with many other aspects of
cellular function, and mitochondria
have a number of other roles. Mitochondria are emerging as a central element in the overall regulation of cell
function; for example, it is becoming
clear that there is constant epigenetic modification of nuclear DNA
according to mitochondrial states,
including the level of production of
oxygen free radicals. Thus, it is not
surprising that they are implicated in
a variety of disease states. The New

Scientist magazine recently summarized a number of examples of mitochondrial function affecting things
other than ATP levels.1 Thus, the
idea that mitochondria do not affect
aspects of a person’s physiology that
contribute to their identity is bound
to be wrong, although our knowledge of these complexities is still rudimentary. A similar claim might be
made about the majority of genes in
the nuclear genome that have ‘housekeeping’ functions. But the attempt
to suggest that mitochondrial function is cleanly separable from other
aspects of cell function in the same
way that mitochondrial DNA is in a
different compartment from nuclear

DNA shows how DNA-centered reductionist biology serves the effort to
convince the public that they did not
need to worry about this form of genetic manipulation.
In examining the way in which
scientifically misleading information
by key scientific authorities has been
used to manipulate the public debate, one is irresistibly reminded of
the example of human-animal hybrid
embryos. In 2007 and 2008, while the
HFEA Act was being updated, the
UK witnessed a massive campaign
by scientists (including several UK
Nobel Prize winners) to legalize the
creation of human-animal hybrid
embryos which, we were told, were
vital to medical research. Despite
warnings by the author that such embryos were worthless for scientific
research, the UK Parliament duly legalized their use. But in the following
year, the Medical Research Council
was forced to reject funding applications from the same research center that is spearheading the push for
mitochondrial replacement because
they lacked scientific merit.
In addition to misleading scientific statements for general public
consumption, the HFEA has also
conducted scientific reviews of the
safety of mitochondrial replacement.
There are many problems with the
review panel’s treatment of these issues, all of which tend in the same direction, towards permitting clinical
trials as soon as possible. The panel
has consistently adopted a standard
of proof that is neither precautionary nor ‘evidence-based,’ but in fact
anti-precautionary: ‘There is no evidence to suggest that the techniques
are unsafe.’ There are certainly plenty of reasons for thinking that the
techniques might be unsafe and one
would have thought that under legislation that makes the welfare of the
child the paramount consideration,
Sept-Nov 2014

a precautionary approach would be
used.
The most obvious safety concern
about these techniques is the possibility that the extremely invasive
manipulation of embryos may damage the embryos, for example by
creating epigenetic problems which
may affect the child’s health. It is well
known that assisted reproductive
technologies can create epigenetic
errors, even when the manipulations
are relatively minor, as in basic IVF.
In general, the more invasive the manipulation, the greater risk of epigenetic problems; the techniques under
consideration would involve the most
invasive manipulations in clinical use
to date. The few published papers on
the mitochondrial replacement techniques clearly show that the manipulations damage the embryos, so that
a relatively low percentage survive to
the blastocyst stage. Given this, it is
reasonable to expect that the surviving embryos will have more subtle
damage, and it is imperative that
comprehensive safety studies focusing on possible epigenetic issues in
these embryos are concluded before
clinical trials are permitted. However,
the HFEA panel merely recommends
such studies rather than requiring
them. The downplaying of these issues is consistent with the DNA-centered reductionist biology which has
already been noted: The regulators,
like the lay public, are assuming that
creating a healthy embryo is simply a
matter of making sure it has the right
DNA.
Bad ethics
The HFEA’s misrepresentation of
ethical issues are too numerous to
detail here; Human Genetics Alert
has prepared an in-depth analysis of
these which is available on request.
In all its materials, where HFEA
Volume 27 Number 3

presented critiques, it either underor over-states the argument, and in
every instance the discussion is presented in the form: “critics claim that
… but others argue that... .” Its treatment of the crucial issue of germ line
manipulation (see article in this issue
by Darnovsky and Cussins) is entirely inadequate. And it entirely fails to
present a conventional risk/benefit
analysis and repeatedly suggests that
the techniques are the only way in
which mothers who carry these conditions can have healthy children. Although the existence of conventional
egg donation as an alternative is very
briefly mentioned, it nowhere acknowledges that this means that the
sole benefit of the new techniques is
that the mother can be the nuclear
genetic parent of her child, and that
this is not a medical benefit to either mother or child, but merely a
social benefit. In our view, given the
safety risks of the techniques, this
social benefit cannot justify exposing a child to the potentially harmful health consequences of the techniques. In my view, it is difficult to
understand the devotion of millions
of pounds of research funding to the
development of techniques which
will deliver such a benefit to a very
small group of people. To cross the
crucial ethical line of non-manipulation of the human genome for such a
benefit is simply absurd.
Despite the HFEA’s bias in favor
of legalization of the techniques, a
strong majority of responses to the
online consultation opposed legalization. However, the HFEA preferred to take notice of the results
of its focus groups and opinion poll,
both of which involved uninformed
participants whose opinions are
easier to manipulate. Recent opinion
polls have contradicted the HFEA’s
opinion poll results and suggested
that less than 20% of the population

actually supports the techniques. Its
press statements glossed over the
negative response to the online consultation and simply declared ‘broad
public support’ for the techniques.
The UK Department of Health has
done the same thing in its consultation on proposed regulations.
Conclusion
The experience of this public consultation process has been depressing for those who would support
democratic control of reproductive
technologies. The supporters of the
techniques created an extremely
well coordinated campaign, exploiting the public’s natural sympathy
for families with sick children. The
‘watchdog’ body acted more like a
cheerleader for the campaign, consistently manipulating both scientific
fact and ethical issues in order to
achieve the desired results, and when
the public response was negative,
simply ignoring that fact. A compliant media failed to raise the critical
issues. It can hardly be claimed that
Britain has undergone the public debate necessary to take a decision of
this historical magnitude.
It is difficult to say whether an unregulated ‘Wild West’ or a technocratic regulator willing to manipulate
facts to achieve its preferred result is
the least desirable environment for
responsible use of reproductive technologies. A better third alternative
must await the advent of a genuine
citizens’ movement on these issues.
nnn
David King, PhD, is a former molecular
biologist and is Director of Human Genetics Alert (www.hgalert.org).

GeneWatch 21

Is Ooplasm Transfer Safe for the
Offspring?
Adapted from testimony submitted to the FDA’s Cellular,
Tissue, and Gene Therapies Advisory Committee.
By Sheldon Krimsky

From comments submitted to the
FDA’s Cellular, Tissue, and Gene
Therapies Advisory Committee, February 25-26, 2014.
The first reported human pregnancy following cytoplasm transfer
from donor oocytes into a woman’s
egg took place in 1997.1 Like many
advances in assisted reproduction,
ooplasm transfer is designed to help
women who seek a healthy pregnancy – a noble endeavor. However, I offer three questions that should be answered before the procedure moves
forward to gain FDA approval and
possibly becomes institutionalized:
1. Is ooplasmic transfer safe and effective for the offspring?
2. If the procedure is found to be
generally safe but with some risks,
do prospective parents have the
authority to undertake the procedure, balancing risks and benefits,
without additional oversight?
3. Are the potential benefits of ooplasm transfer for improving fertility or preventing the transfer
of mitochondrial disease unique
and sufficient to open the door to
germ line genetic modification?
Question 1 is largely scientific;
questions 2 and 3 are largely ethical.
My remarks today address question
1.
Most scientists who specialize
in the biology of reproduction and
22 GeneWatch

who have written about cytoplasmic
transfer have a clear message.
• Cytoplasmic transfer appears to
be consistently associated with
mitochondrial heteroplasmy.2
• Heteroplasmy, or babies born with
two distinct female mitochondrial
genomes, is a risk which must be
understood before cytoplasmic
transfer aka ooplasm transfer is
considered for clinical practice.3
• While an estimated 30 babies have
been born using the technique,
there have been no systematic follow-up studies that examine the
rate and degree of heteroplasmy
in the newborn and in cases where
it exists on its effect on the developmental health of the child.
A recent review in Pub Med for
the terms heteroplasmy and mitochondrial disease had 501 citations,
while ooplasm transfer in human
cells had 58 citations. There is remarkably sparse empirical knowledge in animal studies and almost no
human clinical studies on the safety
and efficacy of ooplasmic transfer.
There are no follow-up studies on
the 30 children born through ooplasmic transfer. As one researcher
wrote: “Transfer of oooplasm was
thus applied with astonishing speed
in humans in the absence of extensive research to evaluate the efficacy
and the possible risks of the method.”
That was written in 2004, and things
haven’t changed.4

The few published animal studies
report a clear and present danger:
• Heteroplasmy created by the mixture of cytoplasm from different
strains of mice resulted in physiological impairment, including
disproportionate weight gain and
cardiovascular system changes.5
• Cytoplasmic transfer used in
cattle produces heteroplasmic
offspring.6
• Some children born through cytoplasmic transfer have been identified as heteroplasmic.7
• There is cross talk between mitochondrial DNA and nuclear DNA;
it is not known but suspected that
nuclear DNA cross talk between
two mitochondrial genomes will
affect the development of the
offspring.8
• The paternal genome may be especially susceptible to epigenetic
alternations by foreign ooplasm.9
• Mixing of two different mouse
mitochondrial DNA within the
same female germline can lead to
offspring with neuro-psychiatric
Sept-Nov 2014

defects.10
• While offering the prospect of
treatment to some infertile couples, cytoplasmic transfer is “capable of generating unexpected
abnormalities.”11
The authors of the most current
and comprehensive review article of
mitochondrial DNA and heteroplasmy, referring to ooplasmic transfer
and other ART procedures, wrote
that “all appropriate preclinical tests
must be performed in an effort to reduce the risk for adverse outcomes.”12
Many questions need to be answered before ooplasmic transfer
could be considered safe and effective to the offspring. Until these
questions are answered first by systematic animal studies,13 I can find
no consensus within the scientific
community to proceed.

Other methods for addressing the
transfer of mitochondrial disease to
offspring, such as Pronuclear Transfer or Maternal Spindle Transfer,
introduce similar problems of heteroplasmy which have not been resolved. As noted by Spikings et al.
(2006): “Other techniques, such as
germinal vesicle transfer and pronuclear transfer, have been proposed
as methods of preventing transmission of mitochondrial diseases to future generations. However, resulting
embryos and offspring may contain
mtDNA heteroplasmy, which itself
could result in mitochondrial disease. It is therefore essential that uniparental transmission of mtDNA is
ensured before these techniques are
used therapeutically.”14
There are ethical questions concerning germ line gene modification

for ooplasm transfer, Pronuclear
Transfer and Maternal Spindle Transfer, which hold equal if not greater
weight than the scientific questions.
These issues should be addressed by
a national ethics commission, which
should assess whether the “threeparent genome” is a stepping stone
to a new eugenics.15
nnn

Sheldon Krimsky, PhD, is Chair of the
Board of Directors of the Council for Responsible Genetics, and the Lenore Stern
Professor of Humanities and Social Sciences in the Department of Urban and
Environmental Policy and Planning and
adjunct professor in the Department of
Public Health and Community Medicine
at Tufts University

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